Since time immemorial, herpes viral infections have been a scourge of mankind and many important domestic animals. The herpes family of virus includes herpes virus simplex (types 1 and 2) responsible for cold sores and genital lesions, respectively; varicella zoster virus which causes chicken pox and shingles; and the Epstein-Barr virus which causes infectious mononucleosis. Although some significant advances have been made in the last decade in antiviral therapy, the need for effective, safe therapeutic agents for treating herpes viral infections continues to exist. For a recent review of current therapeutic agents in this area, see M. C. Nahata, "Antiviral Drugs: Pharmacokinetics, Adverse Effects and Therapeutic Use", J. Pharm. Technol., 3, 100 (1987).
It has now been found that a group of naphthalene derivatives, having a wide margin of safety, are useful for combatting herpes viral infections. The naphthalene derivatives are known having been described previously as antipsoriatic agents, see G. H. Jones et al., U.S. Pat. No. 4,466,981, issued Aug. 21, 1984 and U.S. Pat. No. 4,593,120, issued Jun. 3. 1986. See also G. H. Jones et al., J. Med. Chem. 29, 1504 (1986).
Accordingly, the present invention provides a well tolerated and effective means for preventing or relieving herpes viral infections.
The association of antiviral activity with the above-noted napththalene derivatives is an unusual finding. On a structural basis, it represents a departure from the chemical structures of compounds usually associated with antiviral activity, such as purine and pyrimidine nucleosides, 1-adamatanamine, particular interferons, etc. Two naphthalene derivatives, nevertheless, have previously been reported to have antiviral properties. The two naphthalene derivatives are 1,2,3,4-napththalenetetrone, M. Y. Kraft et al., UK patent 1,243,401, Aug. 18, 1971, and 6-bromo-1,2-naphthalenedione, L. F. Stebaeva et al., Farmakol. Toksikol. (Moscow), 43, 609 (1980); Chem. Abstr., 93, 179724j (1980). The naphthalene derivatives of the present application are distinguished readily from the latter two naphthalene derivatives by marked structural differences arising from the substituents on, and oxidation levels of, their bicyclic structures.